Device, system and method for monitoring a surgical site

ABSTRACT

Embodiments relate to an implantable device for detecting leakage of matter from a mammalian lumen, the device comprising a mesh structure that is attachable to a lumen of a mammalian. The mesh structure comprises a material or a material composition that is electrically conductive and which is measurably responsive in terms of its electrical conductivity when being subjected to leakage of matter from the lumen.

This application claims the benefit of priority from U.S. ProvisionalPatent Application No. 62/192,395, filed on Jul. 14, 2015. The contentof the above document is incorporated by reference in its entirety as iffully set forth herein.

FIELD

Embodiments disclosed herein relate in general to the detection ofleakage from the gastrointestinal system.

BACKGROUND

Various surgical procedures involve removal of a tissue section from thegastrointestinal tract. The removal of a tissue section is followed byre-connecting the remaining tissue portions as in Bariatric surgery orby reconnecting a first tubular tissue portion with another tubulartissue portion, also known as anastomosis, to re-establish tissuecontinuity of the gastrointestinal tract. The reconnection of tissueportions can be performed using surgical staplers or suturing material.The quality of such tissue reconnection and thus the occurrence of leaksis, in general, not surgeon dependent.

As is well known, the presence of leaks at sites where gastrointestinaltissue portions were reconnected can result in significant healthproblems and be potentially devastating. Early diagnosis of the presenceof leaks in a post-surgical setting is thus of paramount importance tominimize morbidity and mortality rates. However, as these sites areinternal to the body, early detection is difficult and/or costly.

The description above is presented as a general overview of related artin this field and should not be construed as an admission that any ofthe information it contains constitutes prior art against the presentpatent application.

SUMMARY

Aspects of disclosed embodiments relate to an implantable device formonitoring a site of biological tissue like, e.g., a surgical siteinside a living body of, e.g., mammalian body such as withoutlimitation, a human body, for example, to detect leakage of body matter(e.g., body fluid) from an organ inside the body Accordingly, suchdevice may be employed for monitoring the integrity of an organ, forexample, for detecting leakage of body fluid from a lumen or cavity ofthe organ.

According to example 1, the device comprises a wire or a mesh structurethat is positionable around an organ (e.g., around a lumen) of amammalian body. The mesh structure comprises a material or a materialcomposition that is electrically conductive and which is measurablyresponsive in terms of its electrical conductivity when being subjectedto leakage of body matter from the body organ.

Example 2 includes the subject matter of example 1 and, optionally,allows direct measurement of changes of an electrical property ofbiological tissue of the body organ.

Example 3 includes the subject matter of examples 1 or 2 and,optionally, wherein the body organ is any one of: the stomach, the smallintestine, the large intestine and/or the esophagus.

Example 4 includes the subject matter of any of the examples 1 to 3 and,optionally, wherein the mesh structure comprises conductive material andbiocompatible and, further optionally, biodegradable material.

Example 5 includes the subject matter of example 4 and, optionally,wherein the biodegradable conductive material is a biodegradableconductive polymer and/or a biodegradable conductive metal.

Example 6 includes the subject matter of example 4 and, optionally,wherein the biodegradable polymer comprises Polypyrrole or anyderivatives thereof.

Example 7 includes the subject matter of example 4 and, optionally,wherein the biodegradable conductive metal comprises magnesium, or acombination thereof.

Example 8 includes a system for monitoring a site within a mammalianbody, comprising an implantable device according to any of the examples1 to 7 and which is configured to be operably attachable to an organinside the mammalian body; and a leak monitoring device which isoperably coupled with the implant and which comprises: a power sourcefor delivering electrical energy to the implant; and a detector enginefor measuring changes in the electrical properties of the implantabledevice.

According to an aspect of some embodiments of the present invention,there is provided an implantable device comprising at least two wires,wherein at least one wire is configured to attach along a site of anorgan, and wherein the at least one wire comprises a biodegradableconductive polymer and/or a biodegradable conductive metal.

In some embodiments, the implantable device is for monitoring biologicaltissue leakage of body matter from an organ (e.g., a body organ or alumen thereof) of a mammalian body.

In some embodiments, the at least two wires are in the form of meshstructure.

In some embodiments, at least one wire is positioned external to thebody organ.

In some embodiments, the biodegradable conductive metal comprises ametal selected from the group consisting of magnesium, iron, zinc andcalcium, or any combination thereof.

In some embodiments, the body organ is the stomach, the small intestine,or the large intestine.

In some embodiments, the biodegradable conductive polymer or thebiodegradable conductive metal is characterized as being measurablyresponsive in terms of its electrical conductivity when being subjectedto body matter leaking from the body organ.

In some embodiments, the body matter is a cytokine or an enzyme.

In some embodiments, the enzyme is metalloproteinase.

In some embodiments, the metalloproteinase is selected from the groupconsisting of MMP-8 and MMP-9.

In some embodiments, the body matter is characterized by a pH value thatvaries within ±0.5.

In some embodiments, the biodegradable conductive polymer or thebiodegradable conductive metal is characterized by a conductivity (S/cm)having a value of 100 to 7,500 S/cm.

According to an aspect of some embodiments of the present invention,there is provided a system for monitoring a site within a mammalianbody, comprising an implantable device according to any of the precedingclaims which is configured to be operably attachable to an organ insidethe mammalian body; and a leak monitoring device which is operablycoupled with the implant and which comprises a power source fordelivering electrical energy to the implant; and a detector engine formeasuring changes in the electrical properties of the implantabledevice.

According to an aspect of some embodiments of the present invention,there is provided a method comprising attaching at least one wire alonga site of an organ, wherein the at least one wire is configured toattach to along a site of an organ, and wherein the at least one wirecomprises a biodegradable conductive polymer and/or a biodegradableconductive metal, the method further comprising monitoring biologicaltissue leakage of body matter from a body organ.

This summary is provided to introduce a selection of concepts in asimplified form that are further described below in the DetailedDescription. This summary is not intended to identify key features oressential features of the claimed subject matter, nor is it intended tobe used to limit the scope of the claimed subject matter.

BRIEF DESCRIPTION OF THE FIGURES

For simplicity and clarity of illustration, elements shown in thefigures have not necessarily been drawn to scale. For example, thedimensions of some of the elements may be exaggerated relative to otherelements for clarity of presentation. Furthermore, reference numeralsmay be repeated among the figures to indicate corresponding or analogouselements. The figures are listed below.

FIG. 1 schematically illustrates a system for the monitoring of asurgical site of a body organ, according to an embodiment;

FIG. 2A schematically illustrates a plan view illustration of animplantable device of the system in an operable position adjunct to atissue reconnection site of the GI tract;

FIG. 2B schematically illustrates the implantable device of FIG. 2Awhere the implantable device's physical properties has undergone changesdue to leakage of body matter from the organ, according to anembodiment; and

FIG. 3 is a flow chart illustration of a method for monitoring theintegrity of an organ, according to an embodiment.

FIG. 4 schematically illustrates the implantable device of FIG. 2A wherethe implantable device is implanted in the colon, according to anembodiment.

DETAILED DESCRIPTION OF EMBODIMENTS

The description is given with reference to particular examples, with theunderstanding that such device, system and method are not limited tothese examples.

Aspects of embodiments disclosed in this description relate to a device,system and method for monitoring the integrity of an organ inside abody, e.g., to detect leakage of body matter from the organ (e.g., thegastrointestinal or GI tract). Such leakage may include post-operativeleakage.

In some embodiments, the device has at least two wires.

In some embodiments, at least one wire is configured to attach along asite of an organ.

In some embodiments, at least wire comprises a biodegradable conductivepolymer and/or a biodegradable conductive metal.

Non-limiting examples of the organ may include any one of the following:the stomach, the small intestine, the large intestine, the esophagus,and/or any other, for example, hollow tubular organ.

It is further noted that the term “detection” as well as grammaticalvariations thereof may encompass any processes that enable such“detection”, including sensing and/or monitoring.

Reference is made to FIG. 1. Generally, a system 100 for monitoring anorgan 101 inside the body, e.g., for detecting leakage of body matterfrom organ 101 through reconnection site 102 at which a first and secondtubular tissue portion 103B and 103A of the organ were reconnected in asurgical procedure, comprises an implantable device 110 and a leakmonitoring device 120 operatively coupled with implantable device 110.

The term “operatively coupled” may encompass the meanings of the terms“responsively coupled”, “communicably coupled”, and the like.

In an embodiment, implantable device 110 may have electrical properties(e.g., conductivity) allowing the device to be employed to monitorchanges in an environment occurring at and/or in the vicinity ofreconnection site 102.

Such environmental change might be indicative of leakage of matter fromthe organ of, e.g., gastrointestinal (GI) tract 101 through reconnectionsite 102 to the outside of the tract or organ, and may for exampleinclude a decrease or increase in pH value, increase in lactateconcentration and/or enzymatic activity, which may for example result inan increase to the implantable device's exposure to inflammatoryresponse, e.g., increase of matrix metalloproteinase enzymes (MMP),interleukin (IL)-6, and/or any other change(s) in an environmentalparameter as further described below. Accordingly, implantable device110 exposed to such environmental changes when being set in an operableposition (for example, topically, e.g., when engaging a biologicaltissue region to overlay a reconnection site) may allow detection ofleakage of body matter from organ 101.

In some embodiments, the term “gastrointestinal tract”, as used herein,is defined as the part of the body which includes the esophagus, stomachand small and large intestines. In some embodiments, the term “topical”,or any grammatical variation thereof, is defined as application to themucosal surfaces of the body and include applications to areas of thegastrointestinal tract.

In some embodiments, the term “metalloproteinase”, or “metalloprotease”,as used herein, may refer to protease enzyme whose catalytic mechanismmay involve a metal.

The term “metalloproteinases” includes, but is not limited to, thecollagenases, gelatinases, stromelysins, matrilysin (MMP-7); enamelysin(MMP-20), macrophage metalloelastase (MMP12), MMP-19 and membrane-typemetalloproteinases (MT-MMP-1 to 4, stromeIysin-3, and MMP-11).

Environmental changes at reconnection site 102 may cause changes to thebiological tissue to which implantable device 110 is attached and, as aresult thereof, correspondingly impact the electrical properties of thetissue.

According to an embodiment, changes in an electrical property ofbiological tissue may be read out and monitored by leak monitoringdevice 120 via implantable device 110 covering a region of the impactedbiological tissue, as outlined in the following.

For instance, implantable device 110 may exhibit at least one electricalproperty which is responsive to body matter or overall inflammatoryresponse that may flow and/or be stored, e.g., in GI tract 101 or in anyother organ and which is measurable by leak monitoring device 120. Forexample, implantable device 110 may comprise material or materials thatare electrically conductive and responsive to body matter that is knownto be flowing within the lumen of a body organ 101 (e.g. GI tract). Forexample, implantable device 110 may undergo structural change(s) whenbeing subjected to or engaging with body matter. These structuralchanges may, for example, include at least partial or full materialdegradation comprised in implantable device 110. Responsive to suchstructural changes, the electrical properties of implantable device 110may be altered. Changes in the electrical properties of implantabledevice 110 may be measured by leak monitoring device 120 using, e.g., DCor AC current. Such readout or measurement of environmental changes mayherein be referred to as “indirect measurement”.

In some embodiments, the electric property refers to current density. Insome embodiments, the current density is calculated from electrodepotential curve(s), i.e. polarization curve(s).

In some embodiments, from such curves it is possible to calculate thenumber of ions per unit time liberated into the tissue as well as thedepth of the metal removed by corrosion for a given time (referred to as“corrosion rate”).

As further described hereinbelow, the corrosion rate can be calculatedand compared with an electrode that is placed outside the regionsuspected to undergo an environmental change, due to e.g., inflammation.The higher the current difference between the electrodes, the higher thechance that inflammation has caused more pronounced degradation and thusmay predict leakage.

In some embodiments, implantable device 110 has a biodegradable portionand an unchanged portion (also referred to herein as: “referenceportion”). In some embodiments, the unchanged portion is used to providea common reference from which structural changes can be measured and/orcalculated. That is, in some embodiments, the measurement refers tochanges in the structure profile of the biodegradable portion.

In some embodiments, the changes measured in the structure profile arecalculated without reference to an area of unchanged topography.

The reference portion may be implanted in the body.

The reference portion and the biodegradable portion may be both locatedwithin the same organ.

The reference may be implanted outside the body. The reference portionmay comprise a metal coated with a polymer.

In some embodiments, detection of leakage is performed by a sequence ofindividual measurements. In some embodiments, the results of severalmeasurements are stored in logic circuit until a desired number of “n”of individual measurements have been accumulated, whereupon an averagemeasured or test value is formed.

Direct measurement may relate to measuring changes of an electricalproperty of biological tissue of an organ, e.g., by operably positioningat least two electrodes (not shown) distantly from one another forallowing electrical DC or AC current to flow from one electrode to theother electrode via the biological tissue.

To simplify the discussion that follows, the monitoring of the integrityof an organ may herein be construed as to comprise indirect and,optionally, direct measurement of the electrical properties ofbiological tissue.

An electrical property (whether acquired through direct or indirectmeasurement) may for example comprise impedance, conductivity, electricpotential difference, capacitance, or any other suitable parameter. Anelectrical property may be measured as function of time.

A change in the electrical property as measured by leak monitoringdevice 120 via implantable device 110 may be indicative of leakage fromorgan 101. For example, if the measured impedance of implantable device110 is above or below an impedance threshold value for a certain periodof time, it may be inferred that leakage is occurring.

While the discussion that follows relates to the detection of leakagethrough tissue reconnection site 102 connecting between tubular tissueportions 103A and 103B, also known as “Anastomosis”, this should by nomeans to be construed as limiting. The system, device and methoddisclosed herein is thus not only suitable to detect anastomotic leakagebut also leakage which may be the result of a surgical procedureincluding, for example, Bariatric surgeries like, e.g., sleevegastrectomy; and/or esophagectomy (for generating a gastric conduit bythe stomach in place of the esophagus).

Reconnection site 102 comprises tissues of either tissue portions 103Aand 103B and a surgical tissue connector assembly for securing opposingends of tissue portions 103A and 103B in a position to bring them influid communication with each other such to re-establish tissuecontinuity of the mammalian body organ. Such connector assembly maycomprise, for example, surgical staples and/or one or more suturethreads.

Implantable device 110 may have a wire-like structure.

Implantable device 110 may have two or more wires. In some embodiments,at least one wire is the reference portion, as defined hereinabove. Insome embodiments, at least one wire may undergo biodegradation upon adefined physiological condition.

In some embodiments, the term “biodegradation” is used to denotehydrolytic, enzymatic and other metabolism-induced decompositionprocesses in the living organism, which result in a gradual dissolutionof at least large parts of the implant.

Implantable device 110 may be fixedly attachable to the outer surface104 of the tissue portions 103A and 103B such to cover, at leastpartially, or fully, reconnection site 102 using, for example, variousfixation elements, e.g., glue, adhesives and/or sutures.

Implantable device 110 may have the form of a mesh-structure.

The term “mesh”, as used herein, may refer to a two- or multidimensionalsemi-permeable structure of closely-spaced holes, which is composed of aplurality of elongated and interconnected elements, such as fibers,strands, struts, spokes, rungs made of a flexible/ductile material,which are arranged in an ordered (matrix, circular, spiral) or randomfashion to form e.g., a two-dimensional sheet or a three-dimensionalobject.

In some embodiments, by “closely-spaced holes” it is meant to refer to aspacing of e.g., 1 mm, 2 mm, 5 mm, 10 mm, 15, mm, 20 mm, 30 mm, 40 mm,50 mm, 60 mm, 70 mm, 80 mm, 90 mm, 100 mm, 110 mm, 120 mm, 130 mm, 140mm, 150 mm, 160 mm, 170 mm, 180 mm, 190 mm, or 200 mm, including anyvalue and range therebetween.

According to some embodiments, certain meshes may be composed of fibrouselements which come in direct physical contact with each other at eachintercrossing junction constituting the mesh.

In some embodiments, the mesh structure comprises or is made ofconductive, biocompatible and/or biodegradable material(s) as describedhereinthroughout.

In some embodiments, the mesh or the wire structure comprises a corestructure coated with conductive, biocompatible and/or biodegradablematerial(s) as described hereinthroughout.

In some embodiments, the core comprises one or more metals.

In some embodiments, the mesh structure comprises non-conductive polymerfibers that are interwoven with conductive, biocompatible and/orbiodegradable material(s) as described hereinthroughout.

In some embodiments, the wire (or the mesh) has a uniformly porousarchitecture so that the degradation can be progressed uniformly.

In some embodiments, the term “mesh” is intended to include an elementhaving an openwork fabric or structure, and may include but is notlimited to, an interconnected network of wire-like segments, a sheet ofmaterial having numerous apertures and/or portions of material removed,or the like. Accordingly, the term “mesh” may also refer to a matrix ora net structure. A wire-like segment may for example comprisemonofilaments and/or braided fibers.

In some embodiments, the mesh has a dimension of 0.1 to 20 mm×0.1 to 20mm, including any value and range therebetween.

The outer surface 104 refers to the tissue surface which is pointingoutwardly from the cavity of organ 101. Conversely, the inner surface105 refers to the tissue surface which defines the boundaries of thelumen of organ 101.

The expression “fully covering” reconnection site 102 as used herein mayrefer to a configuration in which implantable device 110 is installedsuch that matter eventually leaking from organ 101 through an opening atany position of reconnection site 102 will come into contact with one ormore of the wire-like segments of implantable device 110 and cause achange in the electrical properties of implantable device 110. Suchmatter may include liquids, solids and/or matter that is in asolid-fluid two-phase state.

As described hereinthroughout, in an embodiment, implantable device 110may comprise conductive, and/or biodegradable material(s). In the eventof leakage, biodegradable material(s) may, according to an embodiment,degrade quickly enough and to an extent which allows the detection ofleakage from organ 101, e.g., within 6 hours, 3 hours, 1 hour, 30 min,15 min, 10 min, 5 min, 1 min, or 30 seconds, from the moment at whichbody matter starts to leak through reconnection site 102. Further, thematerial(s) of implantable device 110 may be functional to allowdetection of leakage for a time period that spans over, e.g., about atleast e.g., 1 week, 2 weeks, 3 weeks, 4 weeks, or 6 weeks, from the timeimplantable device 110 was set in operable position within the mammalianbody.

According to an embodiment, biodegradable material(s) employed may fullydegrade within mammalian body after a few weeks, 1 month, a few monthsor years (e.g., after 6 months, 1 year, or two years).

Details of example biodegradable material are outlined herein below. Inan embodiment, electrical wiring and/or implantable device 110 may beremovable through a “port” (not shown) having an inner end and an outerend and which is provided in the mammalian body. For example,implantable device 110 may have a collapsible and meshed structurewhich, when being forced against the inner end from outside themammalian body, collapses to attain a wire-like structure allowing itsremoval through the port. The removal may be accomplished as in theextraction of suturing material.

In an embodiment, the diameter of port may be of a magnitude to preventinfections and may for example range from 100 μm to 1 mm or from 100 μmto 4 mm.

As a result of such environmental changes (e.g., changes to or in thevicinity of the biological tissue to which implantable device 110 may beattached), a change in the electrical properties of implantable device110 may occur, which may be detected by leak monitoring device 120. Forexample, and without being limited thereto, a change (e.g., drop) in pHvalue and/or concentration of ionic species may be detected by measuringa corresponding change (e.g., decrease) in the impedance of implantabledevice 110. In some embodiments specific enzymes affect the polymericmesh structure. In some embodiments, pH value and/or concentration ofionic species affect the biodegradable metal.

In some embodiments, the pH value, following the environmental change(e.g., leakage of body matter), varies within less than ±0.5. In someembodiments, the pH value, following the change, varies within less than±0.5 for at least 30 min, at least 1 h, at least 5 h, or at least 10 h.

In an additional non-limiting example, the environmental change refersto pH decrease. In an additional non-limiting example, the environmentalchange refers to an enzymatic activity increase. In an additionalnon-limiting example, the environmental change refers to a cytokineactivity increase. In an additional non-limiting example, theenvironmental change refers to one or more symptoms derived from aninflammatory response e.g., pH, enzymes, oxidative stress, free radicalsetc.

In some embodiments, “activity increase” refers to the increase inconcentration e.g., of the corresponding enzyme or cytokine.

In some embodiments, “activity increase” refers to the increase inconcentration of at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%,12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%, including any value andrange therebetween.

Without being hound by any particular mechanism, these changes inactivity may increase the rate of wire or mesh degradation specificallyat the organ site, and therefore may affect the electrical resistance ofthe wire or the mesh.

In some embodiments, the mesh or the wire structure comprises 2, 3, or 4types of biodegradable conductive polymers and/or metals. Herein, by“type” it is meant to refer to a sensitivity property (e.g.,degradability) of the polymer or the metal to a specific environmentalchange, e.g., an inflammatory disease or condition.

In some embodiments, by “inflammatory disease or condition” it is meantto refer to a local range of concentration of a specific enzyme orcytokine. In some embodiments, by “inflammatory disease or condition” itis meant to refer to a local range of concentration of a combination offactors, e.g., enzymes, cytokines, acidity etc.

In some embodiments, the term “cytokine” refers to a pro-inflammatorycytokine.

Non-limiting exemplary pro-inflammatory cytokines are selected fromIL-1I, IL-3, IL-6, IL-12, p70, IL-17, MIP-1I and RANTES.

As already outlined herein, surgical site monitoring system 100 mayfurther include leak monitoring device 120. According to someembodiments, leak monitoring device 120 may include a processor 121, amemory 122, an input device 123, an output device 124, and a powersource 125 for powering the various components of leakage detectorsystem 100.

The various components of surgical site monitoring system 100 maycommunicate with each other over one or more communication buses (notshown) and/or signal lines and/or communication links (not shown).

Leak monitoring device 120 may be operatively coupled with implantabledevice 110 so that changes of electrical properties of implantabledevice 110 are measurable by leak monitoring device 120, as outlinedherein below in greater detail.

Leak monitoring device 120 may be operative to enable the implementationof a method, process and/or operation for allowing the detection ofleakage from the lumen of organ 101 through a wall to the outside of thetract. Such method, process and/or operation may herein be implementedby a “detector engine” of leak monitoring device 120, referenced byalphanumeric label “126”. Detector engine 126 may be realized by one ormore hardware, software and/or hybrid hardware/software modules, e.g.,as outlined herein. A module may be a self-contained hardware and/orsoftware component that interfaces with a larger system (Alan Freedman,The Computer Glossary 268, (8^(th) ed. 1998)) and may comprise a machineor machines executable instructions.

For example, a module may be implemented as a controller programmed to,or a hardware circuit comprising, e.g., custom VLSI circuits or gatearrays, off-the-shelf semiconductors such as logic chips, transistors,or other discrete components, configured to cause system 100 toimplement the method, process and/or operation as disclosed herein. Amodule may also be implemented in programmable hardware devices such asfield programmable gate arrays, programmable array logic, programmablelogic devices or the like. For example, memory 122, may includeinstruction which, when executed e.g. by the processor 121, may causethe execution of the method, process and/or operation for enabling thedetection of leakage from tract 101. Such method, process and/oroperation may herein be implemented by leak detector engine 126.

According to some embodiments, an input device 123 of a leak monitoringdevice 120 may for example be operatively coupled with implantabledevice 110 e.g., through a plurality of electric wires (e.g., wires 111Aand 111B). The plurality of electric wires may be removable from themammalian body through the port and, as such, may be made or includenon-biodegradable conductive material.

Wires or electrical wiring 111A and 111B may be coupled to implantabledevice 110 so that a sufficiently significant change in the materialproperties of implantable device 110 causes a change in an electricalproperty of the implant measurable by detector engine 126. A detectionof a change in the electrical property of implantable device 110 may beconveyed to a user (not shown) via output device 124. In someembodiments, detector engine 126 may be configured to cause outputdevice 124 to display values (e.g., auditory and/or visually) of theelectrical properties as a function of time, e.g., within a calibratedscale.

In some embodiments, power source 125 may provide electrical energy toimplantable device 110 for measuring changes of the device's electricalproperties so that the magnitudes of electrical energy in the mammalianbody are within physiologically tolerable values. A physiologicallytolerable value may be, for example, an alternating current of 800 μA ata frequency of 50 kHz.

In some embodiments, input device 123 may be equipped with a transmitter(not shown) or a transmitter-receiver (transceiver), e.g., for allowingthe transmission of signals carrying data (“electric-property-data”)that is descriptive of a change of the electrical properties ofimplantable device 110 from input device 123 to a communication module(not shown) of leak monitoring device 120.

It is noted that in some embodiments, one or more components of leakmonitoring device 120 may be internal and one or more components may beexternal to the mammalian body.

For example, input device 123 may be coupled with or include atransmitter (not shown) that may be operably positionable withinmammalian body. Electric-property-data may be transmitted to outsidemammalian body wirelessly over a communication link (not shown) to thecommunication module (not shown) of leak monitoring device 120 forfurther processing.

Leak monitoring device 120 may include a multifunction mobilecommunication device also known as “smartphone”, a personal computer, alaptop computer, a tablet computer, a server (which may relate to one ormore servers or storage systems and/or services associated with abusiness or corporate entity, including for example, a file hostingservice, cloud storage service, online file storage provider,peer-to-peer file storage or hosting service and/or a cyberlocker),personal digital assistant, a workstation, a wearable device, a handheldcomputer, a notebook computer, a vehicular device, a stationary deviceand/or a home appliances control system.

The term “processor” as used herein may additionally or alternativelyrefer to a controller. Such processor may relate to various types ofprocessors and/or processor architectures including, for example,embedded processors, communication processors, graphics processing unit(GPU)-accelerated computing, soft-core processors and/or embeddedprocessors.

According to some embodiments, memory 122 may include one or more typesof computer-readable storage media. Memory 122 may include transactionalmemory and/or long-term storage memory facilities and may function asfile storage, document storage, program storage, or as a working memory.The latter may for example be in the form of a static random accessmemory (SRAM), dynamic random access memory (DRAM), read-only memory(ROM), cache or flash memory. As working memory, memory 122 may, forexample, process temporally-based instructions. As long-term memory,memory 122 may for example include a volatile or non-volatile computerstorage medium, a hard disk drive, a solid state drive, a magneticstorage medium, a flash memory and/or other storage facility. A hardwarememory facility may for example store a fixed information set (e.g.,software code) including, but not limited to, a file, program,application, source code, object code, and the like.

A communication module may for example include I/O device drivers (notshown) and network interface drivers (not shown). A device driver mayfor example, interface with a keypad or to a USB port. A networkinterface driver may for example execute protocols for the Internet, oran Intranet, Wide Area Network (WAN), Local Area Network (LAN)employing, e.g., Wireless Local Area Network (WLAN)), Metropolitan AreaNetwork (MAN), Personal Area Network (PAN), extranet, 2 G, 3 G, 3.5 G, 4G including for example Mobile WIMAX or Long Term Evolution (LTE)advanced, and/or any other current or future communication network,standard, and/or system.

Additional reference is made to FIGS. 2A and 2B. In some embodiments,implantable device 110 may have, as already indicated herein, a meshstructure or body. The mesh structure may, for example, comprise aninterconnected network of wire-like segments 112A and 112B arranged(e.g., perpendicularly) relative to each other, to form a pattern ofpolygons delineating voids in the structure.

Referring to FIG. 2A, the mesh structure of implantable device 110 isshown to be intact, indicative that there is no leakage from the lumenof organ 101 through reconnection site 102 which connects between tissueportions 103A and 103B. When intact, implantable device 110 may haveknown electrical properties such as, for example, electric conductivity.As shown schematically in FIG. 2B, a section 113 of reconnection site102 is shown to be reopened, allowing the leakage of matter 114 from thelumen of organ 101. As a result of the leakage of matter 114,mesh-structure of implantable device may undergo structural changes(e.g., partial or full degradation) in the vicinity of section 113. Thestructural change is schematically illustrated by loose ends 115 ofpreviously continuous wire-like segments 112A and 112B of implantabledevice 110 and indicated at by dashed circles. Due to the structuralchanges of the mesh, the electrical properties of implantable device 110or one of the mesh structure within implantable device 110 may change.Such change in the electrical properties of implantable device 110(e.g., decrease in impedance) may be measurable by leakage engine 126.With respect to such indirect measurement, electrical impedance mayincrease if the material degrades, or even tears or breaks. However,with respect to direct measurement, electrical impedance may dropresponsive to a decrease in pH for example.

According to an embodiment, examples of materials or composition ofmaterials of which implantable device 110 may be made of or may comprisebiodegradable conductive polymers and/or metals; biodegradableconductive polymers and/or metal in combination with and/or next tobiodegradable and/or non-biodegradable non-conductive polymers. In anembodiment, the non-biodegradable residues of implantable device 110 maybe removed through the port (not shown) of the mammalian body.

A combination of the employment of conductive and non-conductivematerials may allow obtaining implantable devices 110 havingrespectively varying electrical properties. An implantable device 110that is intact may for example exhibit an impedance ranging, e.g., up to10²−7.5×10³ (S cm⁻¹).

A combination of biodegradable with non-biodegradable material may allowthe control of the degradation products at the implantation site.

For example, as described hereinabove, change in the electricalproperties of the biodegradable mesh structure within implantable device110 may be measured with respect to a non-biodegradable wire- or meshstructure which is also positioned within implantable device 110.

For example, as described hereinabove, change in the electricalproperties of the conductive mesh structure within implantable device110 may be measured with respect to a non-conductive structure.

The material or composition of materials of which implantable device 110may be made of may be non-toxic, e.g., to allow for it or theirdegradation products to be adsorbed by blood and/or cells of themammalian body. Otherwise stated, material(s) of implantable device 110may exhibit biocompatibility. More specifically, both material(s) ofimplantable device 110 may be biocompatible, as well as the degradationproducts may be biocompatible.

Biodegradable Conductive Polymers:

Non-limiting exemplary polymers for use with the biodegradableconducting polymer of the present invention include but are not limitedto synthetic polymers such as poly (ethylene glycol), Polyglycolic acid(PGA) poly (ethylene oxide), partially or fully hydrolyzed poly(vinylalcohol), polythiophene poly(vinylpyrrolidone), poly(ethyloxazoline),poly(ethylene oxide)-co-poly(propylene oxide) block copolymers,(polpxamers and meroxapols), poloxamines, oxyacetylene,polyparaphenylene, polyparaphenylene sulfide, polyaniline,polyisothionaphthene, polyparavinylene, carboxymethyl cellulose, andhydroxyalkylated celluloses such as hydroxyethyl cellulose andmethylhydroxypropyl cellulose, and natural polymers such aspolypeptides, polysaccharides or carbohydrates, hyaluronic acid,dextran, heparan sulfate, chondroitin sulfate, heparin, or alginate, andproteins such as gelatin, collagen, albumin, ovalbumin or any copolymersor blends thereof.

An example of a conductive polymer that may exhibit desired in-vitro andin-vivo biocompatibility includes the conjugated polymer Polypyrrole(PPy) and/or any derivatives thereof. PPy further exhibits relativelyhigh conductivity under the desired physiological conditions ranging,for example, from 100 to 7,500 S/cm. PPy can be fabricated with highsurface area such as fibers. The primary molecular structure of PPy isshown below:

Examples of secondary molecular structures of PPy are shown below,wherein a plane array of the monomers are predominantly bound by α, α′bonds and to a lesser extent by α, β′; and β,β′ bonds:

In an embodiment, conductive polymers such PPy can be synthesized toform a composite together with a biodegradable polymer. For example, PPymay be synthesized together with a biodegradable polymer to arrive aterodible PPy nanoparticle-polylactide (PLA), or PPy-PLLA composites.After biodegradation of the biodegradable polymer, non-degraded materialmay be removed from the mammalian body, e.g., through the port (notshown). The electrical properties and rate of degradation of thedegradable polymer may be designed by selecting a corresponding ratiobetween the two polymers.

In an embodiment, the conductive polymer may be modified, e.g., byadding ionizable (butyric acid) and/or hydrolysable (butyric ester) sidegroups to the backbone of PPy.

In an embodiment, small chains of PPy that can undergo gradual erosionand renal clearance due to their small size may be electrochemicallysynthesized.

Biodegradable conductive metals:

In an embodiment, the conductive metal is selected from, without beinglimited thereto, Magnesium (Mg), Palladium (Pd), and Iron (Fe).

In an embodiment, magnesium may be employed by implantable device 110for exhibiting suitable thrombogenicity and biocompatibility.

In some embodiments, the term “conductive metal” further refers to alloye.g., Magnesium based alloy such as LAE442 and AZ91D. In someembodiments, the alloy may further comprise one or more elementsselected from, without limitation, zirconium, yttrium, and an earthelement.

In some embodiments, the magnesium alloy further comprises calcium (Ca).In some embodiments, the magnesium alloy further comprises zinc (Zn). Insome embodiments, the magnesium alloy further comprises manganese. Insome embodiments, the magnesium alloy further comprises tin. In someembodiments, the magnesium alloy is in the form of rod or wire.

In some embodiments, the term “magnesium” refers to magnesium hydroxide.In some embodiments, the conductive metal is stable at a desired pHrange.

In an embodiment, a biodegradable material may be iron, e.g, Fe>99.8%.Iron can interconvert between ferric (Fe²⁺) and ferrous (Fe³⁺) ions byaccepting and donating electrons quite readily, which makes it a usefulcomponent for cytochromes, oxygen-binding molecules (e.g., hemoglobinand myoglobin), and/or enzymes.

In another embodiment, the metal (or the alloy) is at least partiallycoated by a protective layer. In some embodiments, the protective layercomprises one or more non-metallic derivatives.

Biodegradable non-conductive polymers in conjunction with biodegradableconductive metal:

In an embodiment, a mesh structure of implantable device 110 may employbiocompatible, biodegradable, and/or non-conductive polymer fibers thatare interwoven with biodegradable conductive metals.

Biodegradable implantable device 110 or a portion thereof can bedegraded with time at a known, pre-designed rate until the completion ofthe healing process, thus, for example, circumventing the need toperform unnecessary surgical procedures to remove the supporting implantand significantly reduce the risks and costs involved.

The biodegradable polymer mesh (materials such as, for example, PGAand/or PLA) may have a profile of, e.g., 100 μm-1 mm in diameter, whilethe metal fibers may have a profile ranging, for example, from 5 to 20μm or 5 to 500 μm.

Non-biodegradable, non-conductive polymers in conjunction withbiodegradable conductive metal:

In an embodiment, a mesh structure of implantable device 110 may employbiocompatible, non-biodegradable, non-conductive polymer fibers such as,without limitation, nylon, polyethylene terephthalate (PET),ultra-high-molecular-weight polyethylene (UHMPE), etc., and may beinterwoven with biodegradable conductive metal fibers. Thenon-biodegradable mesh polymer can serve as a mechanical carrier for thebiodegradable conductive metal.

Further reference is made to FIG. 3. According to an embodiment, amethod for detecting leakage of matter from a mammalian body organ mayinclude, as indicated by box 310, overlaying implantable device 110 ontotissue reconnection site 102 of a mammalian body organ.

The method may further include, as indicated by box 320, providingelectrical energy to implantable device 110.

The method may include, as indicated by box 330, measuring an electricalproperty of implantable device 110.

The method may further include, as indicated by box 340, providing anoutput if a measured electrical property is indicative of a leakage ofmatter through the reconnection site.

The various features and steps discussed above, as well as other knownequivalents for each such feature or step, can be mixed and matched byone of ordinary skill in this art to perform methods in accordance withprinciples described herein. Although the disclosure has been providedin the context of certain embodiments and examples, it will beunderstood by those skilled in the art that the disclosure extendsbeyond the specifically described embodiments to other alternativeembodiments and/or uses and obvious modifications and equivalentsthereof. Accordingly, the disclosure is not intended to be limited bythe specific disclosures of embodiments herein. For example, any digitalcomputer system can be configured or otherwise programmed to implement amethod disclosed herein, and to the extent that a particular digitalcomputer system is configured to implement such a method, it is withinthe scope and spirit of the disclosure. Once a digital computer systemis programmed to perform particular functions pursuant tocomputer-executable instructions from program software that implements amethod disclosed herein, it in effect becomes a special purpose computerparticular to an embodiment of the method disclosed herein. Thetechniques necessary to achieve this are well known to those skilled inthe art and thus are not further described herein. The methods and/orprocesses disclosed herein may be implemented as a computer programproduct such as, for example, a computer program tangibly embodied in aninformation carrier, for example, in a non-transitory computer-readableor non-transitory machine-readable storage device and/or in a propagatedsignal, for execution by or to control the operation of, a dataprocessing apparatus including, for example, one or more programmableprocessors and/or one or more computers. The terms “non-transitorycomputer-readable storage device” and “non-transitory machine-readablestorage device” encompasses distribution media, intermediate storagemedia, execution memory of a computer, and any other medium or devicecapable of storing for later reading by a computer program implementingembodiments of a method disclosed herein. A computer program product canbe deployed to be executed on one computer or on multiple computers atone site or distributed across multiple sites and interconnected by acommunication network.

In the discussion, unless otherwise stated, adjectives such as“substantially” and “about” that modify a condition or relationshipcharacteristic of a feature or features of an embodiment of theinvention, are to be understood to mean that the condition orcharacteristic is defined to within tolerances that are acceptable foroperation of the embodiment for an application for which it is intended.

“Coupled with” means indirectly or directly “coupled with”.

Where applicable, although state diagrams, flow diagrams or both may beused to describe embodiments, the technique is not limited to thosediagrams or to the corresponding descriptions. For example, flow neednot move through each illustrated box or state, or in exactly the sameorder as illustrated and described.

It should be understood that where the claims or specification refer to“a” or “an” element, such reference is not to be construed as therebeing only one of that element.

In the description and claims of the present application, each of theverbs, “comprise” “include” and “have”, and conjugates thereof, are usedto indicate that the object or objects of the verb are not necessarily acomplete listing of components, elements or parts of the subject orsubjects of the verb.

Unless otherwise stated, the use of the expression “and/or” between thelast two members of a list of options for selection indicates that aselection of one or more of the listed options is appropriate and may bemade.

All references mentioned in this specification are herein incorporatedin their entirety by reference into the specification, to the sameextent as if each individual patent was specifically and individuallyindicated to be incorporated herein by reference. In addition, citationor identification of any reference in this application shall not beconstrued as an admission that such reference is available as prior artto the present application.

EXAMPLES

Reference is now made to the following examples, which together with theabove descriptions illustrate some embodiments of the invention in anon-limiting fashion.

Example 1 General Procedure

Reference is now made to FIG. 4 which illustrates a colon as thesurgical site 415A and a mesh 405A being implanted thereon.

In exemplary procedures, two meshes (detection electrode, and referenceelectrode) in a mesh density of 1 to 8 mm×1 to 8 mm and at least 2 mm×2mm opening composed of wires (d=150 μm) are implanted, one (405A) at thesurgical site (415A) and another (405B) at a different location of thecolon (415B) further from the surgical site.

In exemplary procedures, potential or current are measured betweensurgical site, points 410, and/or 420 and references sites, 430, and/or440 and are compared.

In exemplary procedures, an inflammatory response occurs owing to GIleakage that triggers inflammatory cascade which in turn provides highcorrosive environment at the surgical site.

In exemplary procedures, the mesh at the surgical site degrades fastercompared to the reference mesh electrode. The potential (or current)measured between points 410, 420 is higher compared to the potential (orcurrent) measured between points 430, 440.

In exemplary procedures, the potential (or current) is measured rightafter surgery and 2, 3, 4 to 6 days post-surgery.

In additional exemplary procedures, the two electrodes are placed at thesame site during surgery, whereas one electrode known to be lessinfluenced by inflammatory response and its degradation would berelatively stable.

In exemplary procedures, an electrode known to be less influenced byinflammatory response is obtained by its coating thereof with slow(about a year) degradable polymer, or other type of metal/alloy.

In additional exemplary procedures alternating current (AC)electrochemical impedance is measured.

In additional exemplary procedures, the coating is 10-100 μm thickness.

In additional exemplary procedures, the coating is permeable to theelectrolyte solution so as to allow current/potential measurement inrelative to the specific body fluids.

Example 2 MMP-8 and MMP-9 Measurement by Direct Current PolarizationTechnique

General Concept:

In exemplary procedures, the levels of MMP-8 and -9 are measured.

In exemplary procedures, the levels are found to be significantly higherin patients who developed anastomotic leakage, as well as biopsies frompatients with impaired anastomotic healing.

In exemplary procedures, the degradation (also referred to as“corrosion”) model comprises an intermetallic particle, a magnesiumanodic metal, and insulation. The particle plays the role of a cathodein micro-galvanic magnesium corrosion.

In exemplary procedures, magnesium ion concentration sharply increaseson the boundary between the anodic and cathodic region as the pH in thesolution decreases. This shows, without being bound by any particulartheory, that magnesium tends to corrode rapidly in an acid solution ascompared to a neutral or alkaline solution.

Materials

-   -   Mg 99.9%    -   AZ91 magnesium alloy    -   Mg—Ca alloy    -   ZX50 and WZ21 alloys    -   Mg—Zn—Ca    -   Iron (Fe>99.8%)    -   Conductive polymers—polypyrrole (PPy), polyaniline (PANi),        polythiophene.        Media

Data exist in regards to trauma or inflammation that is responsible toenzymes released by cells, such as polymorpho-nuclear leucocytes andconsequently increase rate of degradation in the polymer.

In exemplary embodiments, the control solution has pH 7 and does notcontain enzymes.

In exemplary procedures the test solution comprises 0.1 M NaCl (pH 6).

In additional exemplary embodiments, the test/control solution comprisephosphate buffered saline (PBS) solution.

In additional exemplary embodiments, the test solution contains MMP-1,MMP-2, MMP-8 and MMP-9 in the medium.

Method

In exemplary procedures, during direct current polarization (DCP) testthe voltage is swept at a controlled rate (1 mVs⁻¹) between differentpre-set potentials by regulating the current flowing between the working(Mg) and counter (inert metal) electrode.

In exemplary procedures, open circuit potential (OCP) is recorded beforeDCP for a set period of exposure time that allows the material to“stabilize” with the electrolyte and reach a near steady potential. TheDCP initial voltage is nominally set to commence at values more negativethan (i.e. cathodic to) the OCP, and the scan proceeds to increasinglypositive values (that are anodic to the original OCP).

In exemplary procedures, the DCP results show as a Tafel curve, whichprovides thermodynamic information on corrosion potential (E_(corr)),kinetic information from the corrosion current density (i_(corr)) aswell as relative anodic and cathodic reactions.

Results

In exemplary procedures, the measured E_(corr) is between −1V to 1.6Vand in the control solution and E_(corr) of ˜−1.7V and −2V in testsolution.

In exemplary procedures, the measured i_(corr) in the control solutionis between 2 to 10 μA/cm²) and in the test solution i_(corr) is (20 to30 μA/cm²).

Example 3 Electrochemical Impedance Spectroscopeis

Method

In exemplary procedures, an electrochemical impedance spectroscopy (EIS)technique is used to characterize a magnesium sample using the frequencyresponse of AC polarization of pure magnesium (99.9%) substrate.

EIS uses a range of low magnitude polarizing voltages that cycle from apeak anodic to peak cathodic voltage using a spectra of voltagefrequencies. Capacitance and resistance values are obtained for eachfrequency and can then be used to illuminate a number of phenomena andproperties of the Mg surface.

Results

In exemplary procedures, the impedance in the control solution (seeExample 2) is between 20 and 100 ohm·cm² compared to an impedance ofbetween 1 and 15 at the test solution (see Example 2). This occurs inmore than 50% of the frequency range measured between 10-2 Hz and 105Hz.

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims.

All publications, patents and patent applications mentioned in thisspecification are herein incorporated in their entirety by referenceinto the specification, to the same extent as if each individualpublication, patent or patent application was specifically andindividually indicated to be incorporated herein by reference. Inaddition, citation or identification of any reference in thisapplication shall not be construed as an admission that such referenceis available as prior art to the present invention. To the extent thatsection headings are used, they should not be construed as necessarilylimiting.

The invention claimed is:
 1. An implantable device for detecting leakageof body matter from an organ comprising: a controller, at least twowires operatively connected to the controller, wherein at least one wireof the at least two wires is configured to attach along a site of theorgan, and wherein the at least one wire comprises a biodegradableconductive polymer and/or a biodegradable conductive metal; wherein theat least one wire of the at least two wires, when configured to besubjected to or engaged with the body matter, is configured to undergostructural changes including at least partial material degradation; andwherein the controller is configured to detect leakage of the bodymatter from the organ, based on detection of the structural changes ofthe at least one wire.
 2. The implantable device of claim 1, wherein thecontroller is configured to monitor biological tissue leakage of thebody matter from the organ by detecting leakage of the body matter fromthe organ based on the structural changes of the at least one wire. 3.The implantable device of claim 1, wherein said at least two wires arein a form of mesh structure.
 4. The implantable device of claim 1,wherein at least one wire of the at least two wires is configured to bepositioned external to the site of a body organ.
 5. The implantabledevice of claim 1, wherein said biodegradable conductive metal comprisesa metal selected from a group consisting of magnesium, iron, zinc andcalcium, or any combination thereof.
 6. The implantable device of claim1, wherein said organ is an esophagus, stomach, small intestine, orlarge intestine.
 7. The implantable device of claim 1, wherein saidbiodegradable conductive polymer or said biodegradable conductive metalis characterized as being measurably responsive in terms of anelectrical conductivity of said biodegradable conductive polymer or saidbiodegradable conductive metal when being subjected to the body matterleaking from the organ.
 8. The implantable device of claim 7, whereinsaid body matter is a cytokine or an enzyme.
 9. The implantable deviceof claim 8 wherein said enzyme is metalloproteinase.
 10. The implantabledevice of claim 9 wherein said metalloproteinase is selected from agroup consisting of matrix metalloproteinase (MMP)-8 and MMP-9, or acombination thereof.
 11. The implantable device of claim 1, wherein saidbiodegradable conductive polymer or said biodegradable conductive metalis characterized by a conductivity of 100 to 7,500 S/cm.
 12. Theimplantable device of claim 1, wherein at least one of the at least twowires comprises a reference portion from which structural changes can bemeasured and/or calculated.
 13. A system for monitoring a site within amammalian body, comprising: an implantable device configured to beoperably attachable to an organ inside the mammalian body; andcomprising: at least two wires: wherein at least one wire of the atleast two wires is configured to attach along a site of the organ, andwherein the at least one wire comprises a conductive polymer and/or aconductive metal, wherein the at least one wire of the at least twowires, when configured to be subjected to or engaged with body matter,is configured to undergo structural changes, and the system furthercomprising a leak monitoring device for monitoring leakage of the bodymatter from the organ, the leak monitoring device being operably coupledwith the implantable device and which comprises: a power sourceconfigured to supply electrical energy to the implantable device; and adetector engine configured to detect the structural changes in the atleast one wire resulting from the leakage of the body matter from theorgan by measuring changes in electrical properties of the implantabledevice.
 14. A method comprising: attaching at least one wire along asite of an organ, wherein the at least one wire comprises abiodegradable conductive polymer and/or a biodegradable conductivemetal, wherein at least one of the at least two wires, when beingsubjected to or engaging with body matter, is configured to undergostructural changes including at least partial material degradation; andmonitoring biological tissue leakage of the body matter from the organ,wherein the monitoring comprises performing, by at least one memorystoring executable instructions, and at least one processor executingthe executable instructions: detecting leakage of the body matter fromthe organ based on detection of structural changes of the at least onewire.
 15. The method of claim 14, wherein said organ an esophagus,stomach, small intestine, or large intestine.
 16. The method of claim14, further comprising attaching at least one second wire positionedexternal to the site of the organ.
 17. The method of claim 14, whereinsaid biodegradable conductive polymer or said biodegradable conductivemetal is characterized by a conductivity of 100 to 7,500 S/cm.
 18. Themethod of claim 14 wherein said body matter is a cytokine or an enzyme.19. The method of claim 18, wherein said enzyme is metalloproteinase.20. The method of claim 19, wherein said metalloproteinase is selectedfrom a group consisting of MMP-8 and MMP-9, or a combination thereof.